9-111556631-A-G

Position:

• chr9-111556631-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146109.2(PTGR1):​c.880-6832T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,118 control chromosomes in the GnomAD database, including 8,805 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (8805 hom., cov: 32)
• Consequence: PTGR1 NM_001146109.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248

Genes affected

PTGR1 (HGNC:18429): (prostaglandin reductase 1) This gene encodes an enzyme that is involved in the inactivation of the chemotactic factor, leukotriene B4. The encoded protein specifically catalyzes the NADP+ dependent conversion of leukotriene B4 to 12-oxo-leukotriene B4. A pseudogene of this gene is found on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

ZNF483 (HGNC:23384): (zinc finger protein 483) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTGR1	NM_001146109.2	c.880-6832T>C		intron_variant			NP_001139581.1
ZNF483	NM_001007169.6	c.722-19734A>G		intron_variant			NP_001007170.1
ZNF483	XM_047422864.1	c.722-19734A>G		intron_variant			XP_047278820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTGR1	ENST00000538962.7	c.880-6832T>C		intron_variant		2		ENSP00000440281.1
ZNF483	ENST00000358151.8	c.722-19734A>G		intron_variant		2		ENSP00000350871.4

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48574 AN: 152000 Hom.: 8802 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.320

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.319 AC: 48583 AN: 152118 Hom.: 8805 Cov.: 32 AF XY: 0.311 AC XY: 23167 AN XY: 74374

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.316

Alfa AF: 0.381 Hom.: 11821

Bravo AF: 0.305

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7027778; hg19: chr9-114318911;